Studies on isolated preparations of cardiac tissues (Purkinje fibers, atrial and ventricular muscle fibers) will be conducted with standard intracellular microelectrodes to measure membrane potential and K ion-sensitive microelectrodes to measure intracellular potassium activity. The objectives of the studies will include an explanation 1. of the extent to which the toxic effects of digitalis on electrical activity are caused by inhibition of active transport of Na ion and K ion because of interaction with the sarcolemmal Na ion, K ion ATPase and the extent to which they result from other effects of digitalis on the sarcolemmal ionic conductances and b. the mechanisms responsible for phase 4 depolarization at reduced levels of maximum diastolic potential (i.e., MDP less than 55 mV) and the ability of standard and new antiarrhythmic drugs to modify this abnormal type of automaticity. The overall objectives of the experiments are to provide an improved understanding of the abnormalities in cellular electrophysiology that cause disturbances of cardiac rhythm and conduction and the manner in which drugs act against specific abnormalities of rhythm and conduction.